RBCC

Full text data of SORD

SORD [Confidence: high (present in two of the MS resources)]
Sorbitol dehydrogenase; 1.1.1.14 (L-iditol 2-dehydrogenase)

hRBCD IPI00216057
IPI00216057 sorbitol dehydrogenase sorbitol dehydrogenase membrane n/a 1 n/a n/a 1 n/a n/a n/a 3 n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a 1 not mentioned n/a found at its expected molecular weight found at molecular weight

UniProt Q00796
ID DHSO_HUMAN Reviewed; 357 AA.
AC Q00796; B2R655; J3JZZ5; Q16682; Q9UMD6;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-MAR-2010, sequence version 4.
DT 22-JAN-2014, entry version 155.
DE RecName: Full=Sorbitol dehydrogenase;
DE EC=1.1.1.14;
DE AltName: Full=L-iditol 2-dehydrogenase;
GN Name=SORD;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT THR-269.
RC TISSUE=Liver;
RX PubMed=8088829; DOI=10.1006/geno.1994.1276;
RA Lee F.K., Cheung M.C., Chung S.;
RT "The human sorbitol dehydrogenase gene: cDNA cloning, sequence
RT determination, and mapping by fluorescence in situ hybridization.";
RL Genomics 21:354-358(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANTS LEU-239 AND
RP THR-269.
RX PubMed=7782086; DOI=10.1016/0888-7543(95)80082-W;
RA Iwata T., Popescu N.C., Zimonjic D.B., Karlsson C., Hoeoeg J.-O.,
RA Vaca G., Rodriguez I.R., Carper D.;
RT "Structural organization of the human sorbitol dehydrogenase gene
RT (SORD).";
RL Genomics 26:55-62(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT THR-269.
RX PubMed=9183016; DOI=10.1111/j.1432-1033.1997.00760.x;
RA Carr I.M., Markham A.F., Coletta P.L.;
RT "Identification and characterisation of a sequence related to human
RT sorbitol dehydrogenase.";
RL Eur. J. Biochem. 245:760-767(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-269.
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R.,
RA Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G.,
RA Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A.,
RA Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W.,
RA Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X.,
RA Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K.,
RA Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S.,
RA Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human
RT chromosome 15.";
RL Nature 440:671-675(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-269.
RC TISSUE=Brain, and Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 2-357.
RC TISSUE=Liver;
RX PubMed=2691249; DOI=10.1111/j.1432-1033.1989.tb15240.x;
RA Karlsson C., Maret W., Auld D.S., Hoeoeg J.-O., Joernvall H.;
RT "Variability within mammalian sorbitol dehydrogenases. The primary
RT structure of the human liver enzyme.";
RL Eur. J. Biochem. 186:543-550(1989).
RN [8]
RP PROTEIN SEQUENCE OF 2-21.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [9]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16278369; DOI=10.2164/jandrol.05108;
RA Frenette G., Thabet M., Sullivan R.;
RT "Polyol pathway in human epididymis and semen.";
RL J. Androl. 27:233-239(2006).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=20372835;
RA Szabo Z., Hamalainen J., Loikkanen I., Moilanen A.M., Hirvikoski P.,
RA Vaisanen T., Paavonen T.K., Vaarala M.H.;
RT "Sorbitol dehydrogenase expression is regulated by androgens in the
RT human prostate.";
RL Oncol. Rep. 23:1233-1239(2010).
RN [12]
RP TISSUE SPECIFICITY.
RX PubMed=19423711; DOI=10.1074/jbc.M109.001792;
RA Lanaspa M.A., Andres-Hernando A., Rivard C.J., Dai Y., Li N., Berl T.;
RT "ZAC1 is up-regulated by hypertonicity and decreases sorbitol
RT dehydrogenase expression, allowing accumulation of sorbitol in kidney
RT cells.";
RL J. Biol. Chem. 284:19974-19981(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), AND SUBUNIT.
RX PubMed=12962626; DOI=10.1016/S0969-2126(03)00167-9;
RA Pauly T.A., Ekstrom J.L., Beebe D.A., Chrunyk B., Cunningham D.,
RA Griffor M., Kamath A., Lee S.E., Madura R., Mcguire D., Subashi T.,
RA Wasilko D., Watts P., Mylari B.L., Oates P.J., Adams P.D., Rath V.L.;
RT "X-ray crystallographic and kinetic studies of human sorbitol
RT dehydrogenase.";
RL Structure 11:1071-1085(2003).
CC -!- FUNCTION: Converts sorbitol to fructose. Part of the polyol
CC pathway that plays an important role in sperm physiology. May play
CC a role in the sperm motility by providing an energetic source for
CC sperm (By similarity).
CC -!- CATALYTIC ACTIVITY: L-iditol + NAD(+) = L-sorbose + NADH.
CC -!- COFACTOR: Binds 1 zinc ion per subunit.
CC -!- SUBUNIT: Homotetramer.
CC -!- SUBCELLULAR LOCATION: Mitochondrion membrane; Peripheral membrane
CC protein. Cell projection, cilium, flagellum. Note=Associated with
CC mitochondria of the midpiece and near the plasma membrane in the
CC principal piece of the flagellum. Also found in the epididymosome,
CC secreted by the epididymal epithelium and that transfers proteins
CC from the epididymal fluid to the sperm surface (By similarity).
CC -!- TISSUE SPECIFICITY: Expressed in kidney and epithelial cells of
CC both benign and malignant prostate tissue. Expressed in epididymis
CC (at protein level).
CC -!- INDUCTION: Up-regulated by androgens and down-regulated by
CC castration.
CC -!- MISCELLANEOUS: The polyol pathway is proposed to be involved the
CC cellular toxicity of diabetic hyperglycemia.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family.
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DR EMBL; U07361; AAA66064.1; -; mRNA.
DR EMBL; L29008; AAA80565.1; -; mRNA.
DR EMBL; L29254; AAA80566.1; -; Genomic_DNA.
DR EMBL; L29249; AAA80566.1; JOINED; Genomic_DNA.
DR EMBL; L29250; AAA80566.1; JOINED; Genomic_DNA.
DR EMBL; L29251; AAA80566.1; JOINED; Genomic_DNA.
DR EMBL; L29252; AAA80566.1; JOINED; Genomic_DNA.
DR EMBL; L29253; AAA80566.1; JOINED; Genomic_DNA.
DR EMBL; U67243; AAB61898.1; -; Genomic_DNA.
DR EMBL; U67236; AAB61898.1; JOINED; Genomic_DNA.
DR EMBL; U67237; AAB61898.1; JOINED; Genomic_DNA.
DR EMBL; U67238; AAB61898.1; JOINED; Genomic_DNA.
DR EMBL; U67239; AAB61898.1; JOINED; Genomic_DNA.
DR EMBL; U67240; AAB61898.1; JOINED; Genomic_DNA.
DR EMBL; U67241; AAB61898.1; JOINED; Genomic_DNA.
DR EMBL; U67242; AAB61898.1; JOINED; Genomic_DNA.
DR EMBL; AK312444; BAG35352.1; -; mRNA.
DR EMBL; AC090888; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC091117; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC021085; AAH21085.1; -; mRNA.
DR EMBL; BC025295; AAH25295.1; -; mRNA.
DR PIR; A54674; A54674.
DR RefSeq; NP_003095.2; NM_003104.5.
DR UniGene; Hs.878; -.
DR PDB; 1PL6; X-ray; 2.00 A; A/B/C/D=2-357.
DR PDB; 1PL7; X-ray; 2.20 A; A/B/C/D=2-357.
DR PDB; 1PL8; X-ray; 1.90 A; A/B/C/D=2-357.
DR PDBsum; 1PL6; -.
DR PDBsum; 1PL7; -.
DR PDBsum; 1PL8; -.
DR ProteinModelPortal; Q00796; -.
DR SMR; Q00796; 2-357.
DR IntAct; Q00796; 1.
DR MINT; MINT-5004436; -.
DR STRING; 9606.ENSP00000267814; -.
DR ChEMBL; CHEMBL2275; -.
DR DrugBank; DB00157; NADH.
DR PhosphoSite; Q00796; -.
DR DMDM; 292495088; -.
DR REPRODUCTION-2DPAGE; IPI00216057; -.
DR PaxDb; Q00796; -.
DR PRIDE; Q00796; -.
DR DNASU; 6652; -.
DR Ensembl; ENST00000267814; ENSP00000267814; ENSG00000140263.
DR GeneID; 6652; -.
DR KEGG; hsa:6652; -.
DR UCSC; uc001zul.4; human.
DR CTD; 6652; -.
DR GeneCards; GC15P045315; -.
DR HGNC; HGNC:11184; SORD.
DR HPA; HPA040260; -.
DR HPA; HPA040621; -.
DR MIM; 182500; gene.
DR neXtProt; NX_Q00796; -.
DR PharmGKB; PA36021; -.
DR eggNOG; COG1063; -.
DR HOGENOM; HOG000294670; -.
DR HOVERGEN; HBG005484; -.
DR InParanoid; Q00796; -.
DR KO; K00008; -.
DR OMA; MHNTREI; -.
DR OrthoDB; EOG7DRJ36; -.
DR PhylomeDB; Q00796; -.
DR SABIO-RK; Q00796; -.
DR EvolutionaryTrace; Q00796; -.
DR GeneWiki; SORD; -.
DR GenomeRNAi; 6652; -.
DR NextBio; 25929; -.
DR PRO; PR:Q00796; -.
DR ArrayExpress; Q00796; -.
DR Bgee; Q00796; -.
DR CleanEx; HS_SORD; -.
DR Genevestigator; Q00796; -.
DR GO; GO:0005615; C:extracellular space; TAS:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031514; C:motile cilium; ISS:UniProtKB.
DR GO; GO:0030246; F:carbohydrate binding; NAS:UniProtKB.
DR GO; GO:0003939; F:L-iditol 2-dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0051287; F:NAD binding; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0046370; P:fructose biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006006; P:glucose metabolic process; TAS:UniProtKB.
DR GO; GO:0051160; P:L-xylitol catabolic process; IDA:UniProtKB.
DR GO; GO:0006062; P:sorbitol catabolic process; IDA:UniProtKB.
DR GO; GO:0030317; P:sperm motility; ISS:UniProtKB.
DR Gene3D; 3.40.50.720; -; 1.
DR Gene3D; 3.90.180.10; -; 1.
DR InterPro; IPR013149; ADH_C.
DR InterPro; IPR013154; ADH_GroES-like.
DR InterPro; IPR002085; ADH_SF_Zn-type.
DR InterPro; IPR002328; ADH_Zn_CS.
DR InterPro; IPR011032; GroES-like.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR PANTHER; PTHR11695; PTHR11695; 1.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF00107; ADH_zinc_N; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR PROSITE; PS00059; ADH_ZINC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cell projection; Cilium; Complete proteome;
KW Direct protein sequencing; Flagellum; Membrane; Metal-binding;
KW Mitochondrion; NAD; Oxidoreductase; Polymorphism; Reference proteome;
KW Zinc.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 357 Sorbitol dehydrogenase.
FT /FTId=PRO_0000160817.
FT METAL 45 45 Zinc; catalytic.
FT METAL 70 70 Zinc; catalytic.
FT METAL 71 71 Zinc; catalytic.
FT BINDING 51 51 Substrate (By similarity).
FT BINDING 156 156 Substrate (By similarity).
FT BINDING 299 299 Substrate (By similarity).
FT BINDING 300 300 Substrate (By similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT VARIANT 239 239 Q -> L (in dbSNP:rs55739437).
FT /FTId=VAR_000430.
FT VARIANT 269 269 N -> T (in dbSNP:rs2229659).
FT /FTId=VAR_060351.
FT CONFLICT 5 5 Missing (in Ref. 7; AA sequence).
FT CONFLICT 59 59 N -> D (in Ref. 7; AA sequence).
FT CONFLICT 186 186 M -> E (in Ref. 7; AA sequence).
FT CONFLICT 281 281 T -> S (in Ref. 7; AA sequence).
FT CONFLICT 289 289 I -> T (in Ref. 7; AA sequence).
FT STRAND 10 16
FT STRAND 19 24
FT STRAND 34 44
FT HELIX 46 54
FT STRAND 55 57
FT STRAND 71 79
FT STRAND 91 94
FT STRAND 96 98
FT HELIX 104 107
FT HELIX 111 113
FT STRAND 130 136
FT HELIX 137 139
FT STRAND 140 142
FT HELIX 149 168
FT STRAND 175 179
FT HELIX 183 194
FT STRAND 198 205
FT HELIX 207 215
FT STRAND 219 223
FT HELIX 229 240
FT STRAND 245 249
FT HELIX 254 263
FT STRAND 269 272
FT HELIX 284 289
FT STRAND 293 296
FT HELIX 304 312
FT HELIX 319 321
FT STRAND 322 327
FT HELIX 328 330
FT HELIX 331 339
FT STRAND 344 349
SQ SEQUENCE 357 AA; 38325 MW; FF13DDD5EBE47754 CRC64;
MAAAAKPNNL SLVVHGPGDL RLENYPIPEP GPNEVLLRMH SVGICGSDVH YWEYGRIGNF
IVKKPMVLGH EASGTVEKVG SSVKHLKPGD RVAIEPGAPR ENDEFCKMGR YNLSPSIFFC
ATPPDDGNLC RFYKHNAAFC YKLPDNVTFE EGALIEPLSV GIHACRRGGV TLGHKVLVCG
AGPIGMVTLL VAKAMGAAQV VVTDLSATRL SKAKEIGADL VLQISKESPQ EIARKVEGQL
GCKPEVTIEC TGAEASIQAG IYATRSGGNL VLVGLGSEMT TVPLLHAAIR EVDIKGVFRY
CNTWPVAISM LASKSVNVKP LVTHRFPLEK ALEAFETFKK GLGLKIMLKC DPSDQNP
//

MIM 182500
*RECORD*
*FIELD* NO
182500
*FIELD* TI
*182500 SORBITOL DEHYDROGENASE; SORD
;;SORBITOL DEHYDROGENASE 1; SORD1
SORBITOL DEHYDROGENASE 2, INCLUDED; SORD2, INCLUDED
read more*FIELD* TX

DESCRIPTION

Sorbitol dehydrogenase (SORD; EC 1.1.1.14) catalyzes the interconversion
of polyols and their corresponding ketoses, and together with aldose
reductase (ALDR1; 103880), makes up the sorbitol pathway that is
believed to play an important role in the development of diabetic
complications. The first reaction of the pathway (also called the polyol
pathway) is the reduction of glucose to sorbitol by ALDR1 with NADPH as
the cofactor. SORD then oxidizes the sorbitol to fructose using NAD(+)
cofactor (summary by Carr and Markham, 1995).

CLONING

Lee et al. (1994) cloned and sequenced cDNA for human SORD. They found
that it translates into a peptide of 356 amino acid residues, 1 more
than the sequence previously reported from peptide analysis.

Iwata et al. (1995) cloned a human SORD cDNA as well as the gene. The
promoter was shown to contain a CACCC box and 3 putative binding sites
for the transcription factor Sp1 (SP1; 189906). Two alternative
transcription initiation sites were identified. Northern blots
demonstrated expression in most tissues and at particularly high levels
in the kidney and lens of the eye.

GENE FUNCTION

Carr and Markham (1995) noted that the polyol pathway is particularly
active in hyperglycemic states. Although SORD is closely related to the
class I long-chain alcohol dehydrogenases, it differs in substrate
specificity, catalyzing polyols such as sorbitol and xylitol but having
no activity towards primary alcohols.

GENE STRUCTURE

Iwata et al. (1995) determined that the SORD gene is divided into 9
exons spanning approximately 30 kb.

Carr and Markham (1995) defined the intron/exon boundaries of the SORD
gene and identified a number of polymorphic variants.

MAPPING

Donald et al. (1980) assigned the sorbitol dehydrogenase gene to
chromosome 15pter-q21 by somatic cell hybridization.

By fluorescence in situ hybridization (FISH), Lee et al. (1994) mapped
the SORD gene to a single site on 15q15, indicating that it is a
single-copy gene. The localization was confirmed by Southern blot
hybridization in somatic cell hybrids.

Iwata et al. (1995) mapped the SORD gene by FISH to 15q21.1.

Carr and Markham (1995) confirmed the localization of SORD to chromosome
15 by screening somatic cell hybrid mapping panels by PCR and
regionalized the gene to 15q15 by FISH.

- SORD2

Carr et al. (1998) established that 2 very closely homologous SORD
sequences lie within 0.5 Mb on chromosome 15. The SORD2 and SORD1 genes
are oriented head-to-head in the order cen--SORD2--SORD1--tel. Thus the
2 genes appear to represent an inverted repeat with their 5-prime ends
closest together. By fluorescence in situ hybridization, Carr et al.
(1998) showed that both genes are located at 15q15.3.

EVOLUTION

- SORD2

The duplicated human sequences SORD1 and SORD2 translate into proteins
that differ by only 6 amino acid substitutions in their 335 residues,
with a single-nucleotide deletion in exon 7 of SORD2, the apparent loss
of exon 1 from SORD2, and an Alu insertion in intron 8 of SORD2 (Carr et
al., 1997). To establish when the human SORD duplication occurred, Carr
et al. (1998) sequenced the open reading frame of marmoset liver SORD.
SORD appeared to be a single gene in this New World monkey. They found
that marmoset SORD showed significantly less homology with either SORD1
or SORD2 than the 2 do with each other, suggesting that the human
homologs represent a recent gene duplication event. Carr et al. (1998)
presented a hypothesis to explain the retention of the redundant SORD2
sequence in the human genome. All evidence seems to point to the
conclusion that SORD2 is not transcribed, i.e., is nonfunctional (Carr,
1999).

MOLECULAR GENETICS

Op't Hof (1969) stated that 'preliminary studies with human postmortem
liver specimens suggest that a polymorphism for SDH isoenzymes exists
also in man.' Such was indeed found by Charlesworth (1972). Vaca et al.
(1982) described an 'activity polymorphism' of red cell sorbitol
dehydrogenase in a Mexican family, ascertained because of bilateral
cataracts in 4 of 5 brothers and the father. SORD was assayed because
this enzyme converts sorbitol to fructose and sorbitol is implicated in
diabetic cataracts. Because of the incomplete correlation of cataracts
and SORD deficiency in this family, an etiopathogenic relationship could
not be established. Through routine screening, Shin et al. (1984) found
SORD deficiency in a family with congenital cataracts. The cataract
patients in this family showed a residual activity that was 15 to 20% of
the values in healthy subjects. The patients with low values were all
male in this family as in the family reported by Vaca et al. (1982).

Carr and Markham (1995) stated that the accumulation and toxicity of
sorbitol in specific tissues has been implicated in the development of
microvascular problems in some diabetic patients. Inappropriate sorbitol
accumulation in some patients may be the result of polymorphic variation
in the human SORD gene, causing reduced expression levels or enzymatic
activity.

*FIELD* RF
1. Carr, I. M.: Personal Communication. Leeds, England 3/1/1999.

2. Carr, I. M.; Markham, A. F.: Molecular genetic analysis of the
human sorbitol dehydrogenase gene. Mammalian Genome 6: 645-652,
1995.

3. Carr, I. M.; Markham, A. F.; Coletta, P. L.: Identification and
characterisation of a sequence related to human sorbitol dehydrogenase. Europ.
J. Biochem. 245: 760-767, 1997.

4. Carr, I. M.; Whitehouse, A.; Coletta, P. L.; Markham, A. F.: Structural
and evolutionary characterization of the human sorbitol dehydrogenase
gene duplication. Mammalian Genome 9: 1042-1048, 1998.

5. Charlesworth, D.: Starch-gel electrophoresis of four enzymes from
human red blood cells: glyceraldehyde-3-phosphate dehydrogenase, fructoaldolase,
glyoxalase II and sorbitol dehydrogenase. Ann. Hum. Genet. 35: 477-484,
1972.

6. Donald, L. J.; Wang, H. S.; Hamerton, J. L.: Assignment of the
sorbitol dehydrogenase locus to human chromosome 15pter-q21. Biochem.
Genet. 18: 425-431, 1980.

7. Iwata, T.; Popescu, N. C.; Zimonjic, D. B.; Karlsson, C.; Hoog,
J.-O.; Vaca, G.; Rodriguez, I. R.; Carper, D.: Structural organization
of the human sorbitol dehydrogenase gene (SORD). Genomics 26: 55-62,
1995.

8. Lee, F. K.; Cheung, M. C.; Chung, S.: The human sorbitol dehydrogenase
gene: cDNA cloning, sequence determination, and mapping by fluorescence
in situ hybridization. Genomics 21: 354-358, 1994.

9. Op't Hof, J.: Isoenzymes and population genetics of sorbitol dehydrogenase
(EC: 1.1.1.14) in swine (Sus scrofa). Humangenetik 7: 258-259, 1969.

10. Shin, Y. S.; Rieth, M.; Endres, W.: Sorbitol dehydrogenase deficiency
in a family with congenital cataracts. J. Inherit. Metab. Dis. 7
(suppl. 2): 151-152, 1984.

11. Vaca, G.; Ibarra, B.; Bracamontes, M.; Garcia-Cruz, D.; Sanchez-Corona,
J.; Medina, C.; Wunsch, C.; Gonzalez-Quiroga, G.; Cantu, J. M.: Red
blood cell sorbitol dehydrogenase deficiency in a family with cataracts. Hum.
Genet. 61: 338-341, 1982.

*FIELD* CN
Victor A. McKusick - updated: 3/4/1999
Victor A. McKusick - updated: 2/26/1999
Alan F. Scott - updated: 9/26/1995

*FIELD* CD
Victor A. McKusick: 6/2/1986

*FIELD* ED
alopez: 03/07/2012
alopez: 3/5/2012
alopez: 7/20/2010
carol: 3/24/1999
mgross: 3/10/1999
carol: 3/4/1999
terry: 2/26/1999
joanna: 5/8/1998
mark: 10/23/1995
mark: 9/26/1995
carol: 6/29/1994
jason: 6/8/1994
supermim: 3/16/1992
supermim: 3/20/1990

RBCC Red Blood Cell Collection

Full text data of SORD